Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study

Abstract

Rationale & objective: Patients with glomerular disease (GN) may be at increased risk of severe COVID-19, yet concerns over vaccines causing disease relapse may lead to vaccine hesitancy. We examined the associations of COVID-19 with longitudinal kidney function and proteinuria and compared these with similar associations with COVID-19 vaccination.

Study design: Observational cohort study from July 1, 2021, to January 1, 2023.

Setting & participants: A prospective observational study network of 71 centers from North America and Europe (CureGN) with children and adults with primary minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy.

Exposure: COVID-19 and COVID-19 vaccination.

Outcome: Repeated measure of estimated glomerular filtration rate (eGFR); recurrent time-to-event outcome of GN disease worsening as defined by doubling of the urinary protein-creatinine ratio (UPCR) to at least 1.5g/g or increase in dipstick urine protein by 2 ordinal levels to 3+(300mg/dL) or above.

Analytical approach: Interrupted time series analysis for eGFR. Prognostic matched sequential stratification recurrent event analysis for GN disease worsening.

Results: Among 2,055 participants, 722 (35%) reported COVID-19 infection; of these, 92 (13%) were hospitalized, and 3 died (<1%). The eGFR slope before COVID-19 infection was-1.40mL/min/1.73m² (± 0.29 SD); within 6 months after COVID-19 infection, the eGFR slope was-4.26mL/min/1.73m² (± 3.02 SD), which was not significantly different (P=0.34). COVID-19 was associated with increased risk of worsening GN disease activity (HR, 1.35 [95% CI, 1.01-1.80]). Vaccination was not associated with a change in eGFR (-1.34mL/min/1.73m²±0.15 SD vs-2.16mL/min/1.73m²±1.74 SD; P=0.6) or subsequent GN disease worsening (HR 1.02 [95% CI, 0.79-1.33]) in this cohort.

Limitations: Infrequent or short follow-up.

Conclusions: Among patients with primary GN, COVID-19 infection was severe for 1 in 8 cases and was associated with subsequent worsening of GN disease activity, as defined by proteinuria. By contrast, vaccination against COVID-19 was not associated with change in disease activity or kidney function decline. These results support COVID-19 vaccination for patients with GN.

Plain-language summary: In this cohort study of 2,055 patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy, COVID-19 resulted in hospitalization or death for 1 in 8 cases and was associated with a 35% increase in risk for worsening proteinuria. By contrast, vaccination did not appear to adversely affect kidney function or proteinuria. Our data support vaccination for COVID-19 in patients with glomerular disease.

Keywords: COVID-19; COVID-19 vaccines; IgA glomerulonephritis; focal segmental glomerulosclerosis; glomerular filtration rate; glomerulonephritis; lipoid nephrosis; membranous glomerulonephritis; vaccination.

Figure 1.. COVID-19 case counts over calendar time among surveyed CureGN study participants with primary glomerular disease, compared to US COVID-19 counts.

Count of COVID-19 infections per day in CureGN (left y-axis, blue solid line) and the US (right y-axis, in millions of cases, red dashed line).

Figure 2.. Cross-sectional COVID-19 vaccination status (one dose) of CureGN study participants since January 2020.

Vaccination status determined by participant self-report and review of medical records at each study visit. Data were assessed in quarterly intervals. Solid bars (up) indicate % reporting at least one COVID-19 vaccination by age group, while hatched bars (down) indicate % not reporting at least one COVID-19 vaccination, by age group. Table at the bottom shows n (%) in each category for each bar.

Figure 3.. Estimated GFR trajectory among A) CureGN participants who experienced COVID-19, B) CureGN participants who received at least one COVID-19 vaccine.

Results from segmented mixed effects linear regression model, with COVID-19 (A) or COVID-19 vaccination (B) as the “interruption” in the trajectory of eGFR over time, among participants with self-reported COVID-19 (A) or COVID-19 vaccination (B) and at least two eGFR values before and after the interruption event. Models included participant-specific intercepts and slopes. Estimated mean (standard deviation, SD) eGFR value and mean (SD) change in eGFR slope (ml/min/1.73m² per year) before and after the interruption are given on the right.